Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer
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Human papillomavirus (HPV) type 16 infection is an etiologic factor in a subset of head and neck squamous cell carcinomas (HNSCC). It is unknown if host genetic susceptibility modifies the HPV16-HNSCC association. DNA samples collected as part of a Boston area case-control study of HNSCC were genotyped for single-nucleotide polymorphisms (SNPs) from the National Cancer Institute's SNP500Cancer database. Analysis of demographic, phenotypic and genotypic data for 319 HNSCC cases and 495 frequency-matched controls was performed using unconditional logistic regression. All reported P-values are two sided. We identified a polymorphism in the sodium-dependent vitamin C transporter SLC23A2 that modifies the risk of HNSCC associated with HPV16 infection. Among those with a wild-type allele at SLC23A2, the risk of HNSCC associated with HPV16-positive serology was 5.0 (95% confidence interval (CI) = 3.2-7.8). However, among those with a homozygous variant genotype, the risk of HNSCC associated with HPV16 was attenuated [odds ratio (OR) = 2.8; 95% CI = 1.2-6.2]. Further, when we tested whether genotype modified the interaction between citrus exposure, HPV16, and HNSCC, we found a dramatically increased risk of HNSCC for those with a wild-type SLC23A2 allele, HPV16-positive serology and high citrus intake (OR = 7.4; 95% CI = 3.6-15.1). These results suggest that SLC23A2 genetic variation alters HPV16-associated HNSCC while also highlighting the important role of citrus exposure in this disease.
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Common variations of SLC23A2 are linked to HPV16-positive head and neck cancer.
“Common variations of SLC23A2 were linked to increased or decreased risk of gastric cancer depending on a discrete genotype [85,90], decreased risk of colorectal adenocarcinoma [91], HPV16-positive head and neck cancer [92], increased risk of bladder cancer [93], non-Hodgkin lymphoma [87], chronic lymphocytic leukemia [94], preterm delivery [84], open-angle glaucoma [95], and acute coronary syndrom”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [92]
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(2010) · Current Opinion in Otolaryngology & Head & Neck Surgery · doi:10.1097/moo.0b013e3283383ef9
Race as a Social Construct in Head and Neck Cancer Outcomes
Worsham, M. J., Divine, G., & Kittles, R. A. (2010) · Otolaryngology · doi:10.1016/j.otohns.2010.06.094
Yin, B., Li, M.-J., Sun, J., You, Y., Zhang, S.-D., Wan, Q.-X., Yao, M.-L., Yang, C., Sun, H., Lin, Z., et al. (2025) · Journal of Human Genetics · doi:10.1038/s10038-025-01352-y
- Authors
- Chen, A. A., Marsit, C. J., Christensen, B. C., Houseman, E. A., McClean, M. D., Smith, J. F., Bryan, J. T., Posner, M. R., Nelson, H. H., & Kelsey, K. T.
- Affiliations
- Brigham and Women's Hospital (US)
- Brown University (US)
- Boston University (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Dana-Farber Cancer Institute (US)
- University of Minnesota (US)
- Corresponding author
- Kelsey, K. T.
- ORCID
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-04-03
- Volume
- 30
- Issue
- 6
- Pages
- 977-981
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- PMC
- PMC2691140
- OpenAlex
- W2120584959
- Cited by
- 57
- References
- 33
- Citations by year
- 2025: 3 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 3 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 1 · 2014: 9 · 2013: 7 · 2012: 8
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Carcinogenesis (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Merck
- National Institutes of Health (5t32es007155-24)
- National Cancer Institute (T32 CA09001, CA 78609, CA100679, R01CA100679, R01CA078609, T32CA009001)
- National Institute of Environmental Health Sciences (T32-ES07155, T32-ES007155)
- Topics
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- SLC23A2, vitamin C transporter, HPV16, head and neck squamous cell carcinoma, genetic susceptibility, single nucleotide polymorphisms, host-virus interaction, cancer risk modification
- MeSH terms
- Aged, Citrus, Diet, Female, Head and Neck Neoplasms, Humans, Male, Middle Aged, Risk, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Symporters, Organic Anion Transporters, Sodium-Dependent, Papillomavirus Infections, Human papillomavirus 16, Sodium-Coupled Vitamin C Transporters
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